Chen, P., Li, B., & Ou-Yang, L. (2022). Role of estrogen receptors in health and disease. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2022.839005
Chen P, Li B, Ou-Yang L. Role of estrogen receptors in health and disease. Frontiers in Endocrinology. 2022. doi:10.3389/fendo.2022.839005
Chen, Peng, et al. "Role of estrogen receptors in health and disease." Frontiers in Endocrinology, 2022.
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Free full text on PubMed Central (PMC9433670)
RRM Academy Synopsis
Three estrogen receptors have different roles across organs
A 2022 narrative review of lab and human studies finds that three estrogen receptors, ERα, ERβ and GPER1, do different jobs in different organs, endometriosis included. Depending on the organ, ERα is often linked to promoting disease, ERβ to protection, and GPER1 to mixed effects. The authors flag many areas where evidence is unclear.
Key Findings
Estrogen signaling through receptors inside the cell takes hours or more to change gene activity. Rapid effects at the cell membrane, which include GPER1, occur within seconds to minutes.
Endometriosis lesions carry more ERα than normal endometrium, and the amount varies with the menstrual cycle. A study in ERα-knockout mice suggested ERα participates in forming endometriotic-like lesions.
Lesion tissue also carries more ERβ than normal endometrium, and GPER1 is reportedly higher in ovarian endometriosis. Adding the GPER1 agonist G1 stimulated endometriotic cell proliferation.
In breast tissue, ERα expression is approximately 10% in healthy tissues and 50–80% in cancer tissues. The authors call the role of ERβ in breast cancer controversial.
The authors conclude the role of ERs in many diseases, gastric diseases among them, remains unclear or controversial.
Interpretation
The paper is a narrative review. The authors summarize published studies and describe no search method or pooled analysis. Much of the cited work uses mice, rats, rabbits and cell lines, and the review's own table marks which studies involved humans. Animal and cell studies point to mechanisms and associations. The endometriosis section rests on a mouse model and cell experiments, and the review describes no treatment trial in people with endometriosis.
RRM Context
Estrogen receptors sit in the uterus, ovary, bone and brain, and in male tissue. The review says estrogen also helps regulate sperm production and male fertility. Restorative reproductive medicine seeks the root cause and evaluates both partners. The endometriosis receptor findings come from lab models, so the biology is still under study.
Our editorial summary of this paper, not the article's abstract.
Abstract
Estrogen receptors (ERs) regulate multiple complex physiological processes in humans. Abnormal ER signaling may result in various disorders, including reproductive system-related disorders (endometriosis, and breast, ovarian, and prostate cancer), bone-related abnormalities, lung cancer, cardiovascular disease, gastrointestinal disease, urogenital tract disease, neurodegenerative disorders, and cutaneous melanoma. ER alpha (ERα), ER beta (ERβ), and novel G-protein-coupled estrogen receptor 1 (GPER1) have been identified as the most prominent ERs. This review provides an overview of ERα, ERβ, and GPER1, as well as their functions in health and disease. Furthermore, the potential clinical applications and challenges are discussed.
